Break Wave lithotripsy to fragment large kidney stones

SUMMARY Kidney stone surgeries carry 5-20% morbidity; that is between 1-in-5 and 1-in-20 patients return for moderate or severe adverse events requiring further intervention. Our noninvasive, nonsurgical treatment for stones – burst wave lithotripsy (BWL) – has been successfully tested with ≤10 mm stones, with no moderate or serious adverse events. Our proposal is to expand our technology to fragment larger stones in the 10-20 mm range, and preclinically, to test effectiveness and safety. BWL (marketed as Break Wave therapy) transmits a long, narrowband ultrasound tone burst to break the stones as opposed to shock wave lithotripsy (SWL) that sends a short, broadband impulse. In collaboration with Caltech on a previous SBIR grant, we used linear elastic numerical modeling to show that a frequency of 200 ± 50 kHz will generate the highest internal stress to fragment 10-20 mm stones, while higher frequency is more effective for smaller stones. The first challenge is that transducer size tends to scale inversely with frequency, making a traditional 200-kHz transducer too large. To develop a low-frequency (~200 kHz), high-pressure (> 6 MPa) transducer with a compact (< 90 mm diameter) form factor, we will investigate several new technologies, including a porous ceramic element encased in oil, multi- layer stacked transducer designs, and 1-3 composites. The second challenge is that 200 kHz is expected to yield ~3.5 mm fragments. Whereas our current clinical system operating at 350 kHz creates ~2 mm fragments, which are more comfortable to pass with the urine. We will investigate the possibility of using low frequency to coarsely fragment stones and then apply our current clinical frequency and transducer to “dust” the coarse fragments to a small size. The third challenge is that lower frequency increases the risk of cavitation which inhibits treatment and causes injury. Our plan is to refine the proprietary interleaved pulses to suppress cavitation at low frequency. Our overall hypothesis is therefore sequenced 200-kHz then 350-kHz BWL with interleaved pulses will safely fragment stones to 2 mm fragments. The specific aims are 1) Fragment 10-20 mm stones in-vitro with low frequency (Phase 1), 2) Fragment 10-20 mm stones to < 2 mm fragments using two BWL frequencies, 3) Fragment 10-20 mm stones in vivo in porcine model, 4) Measure potential injury in clinical simulation in a porcine model. The innovation leverages our novel treatment modality and advances transducer technology and cavitation suppression. The expected outcome is a safe and effective treatment ready for clinical trials. The impact is a product line to treat 98% of stone sizes in the office without surgery.